Synthesis of fluorine analogues of protoporphyrin potentially useful for diagnosis and therapy of tumors.
With the aim of obtaining a porphyrin derivative useful for diagnosis and therapy of cancer, fluorine analogues of protoporphyrin, in which the vinyl group(s) were replaced by difluorovinyl group(s), were synthesized by the reaction of the formylporphyrins with sodium chlorodifluoroacetate in the presence of triphenylphosphine. Some improvements in the reported procedures for the synthesis of formylporphyrins are also described. Preliminary results of biological tests of the products showed that 8(2),8(2)-difluoroprotoporphyrin accumulates to gastric cancer more selectively than other fluorine analogues and that 3(2),3(2),8(2),8(2)-tetrafluoroprotoporphyrin is taken up by rat hepatoma cells more readily than the others.
Ando
A
A
Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan.
Shinada
T
T
Kinoshita
S
S
Arimura
N
N
Koyama
M
M
Nagai
T
T
Miki
T
T
Kumadaki
I
I
Sato
H
H
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D009368:Neoplasm Transplantation; D011524:Protoporphyrins / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051381:Rats; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured / Q000378:metabolism
D000970:Antineoplastic Agents; D011524:Protoporphyrins; C067200:3(2),3(2),8(2),8(2)-tetrafluoroprotoporphyrin dimethyl ester; C067199:8(2),8(2)-difluoroprotoporphyrin dimethyl ester; C067198:3(2),3(2)-difluoroprotoporphyrin dimethyl ester